Blood cancer gene therapies enter the clinic

The latest listings on the clinicaltrials.gov registry include the entry into human studies of in vivo Car-T therapies in development by Interius BioTherapeutics and Umoja Biopharma, as well as a third private US biotech, Vironexis Biotherapeutics, working on a related gene therapy approach.

Also noteworthy are two inhibitors of CHK1, a checkpoint kinase thought to play a role in DNA damage response that was the lead focus of Boundless Bio’s ill-fated Nasdaq flotation in March. The Umoja and Interius projects, UB-VV111 and INT2104 respectively, are of special interest as they will become the first ever in vivo generated Car-T therapies to start human studies.

UB-VV111 is partnered with AbbVie, which can opt in to development at any point. It works by stimulating production in a patient’s body of an anti-CD19 Car more quickly and conveniently than a typical ex vivo Car-T therapy, and without the need for harsh lymphodepletion, Umoja recently told ApexOnco.

There are only a few in vivo Car-T projects in development. Interius Biotherapeutics’ INT2104, which targets not CD19 but CD20, was last month cleared to start an Australian phase 1 study, which according to clinicaltrials.gov will begin one month before Umoja's. Other players include Sanofi and the private Capstan Therapeutics, while Sana is notable for having floated on the basis of this approach, but then abandoned it entirely.

Somewhat related to UB-VV111 and INT2104 is Vironexis’s VNX-101, a gene therapy that stimulates in vivo production not of a Car construct but of an anti-CD19 bispecific T-cell engager. Clinicaltrials.gov reveals that this will start phase 1 next month. BioNTech is working on a similar approach, BNT142, which comprises mRNA encoding an anti-Claudin6 CD3-based T-cell engager.

CHK1 inhibition

In the small-molecule space, meanwhile, Fosun and Sumitomo are both targeting CHK1, starting human trials of XS-02 and SMP-3124 respectively; the latter is unusual in being encapsulated in liposomes for parenteral delivery.

Sumitomo has said that liposomal encapsulation is designed to change the parent molecule’s pharmacokinetics after initial development as an oral tablet was halted owing to toxicity. OncologyPipeline reveals nine other clinical-stage CHK1 inhibitors in development, including LY2880070, a molecule originated by Lilly and now in development by Esperas Pharma as ESP-001.

Also of note is Boundless Bio, which floated in March and is primarily focused on the CHK1 inhibitor BBI-355; however, Boundless’s stock has lost 80% since the IPO. Fosun’s XS-02 was profiled at AACR this year, and this molecule is delivered orally.

A much more unusual target, LIPA, is the subject of ERX-315, which is due to start an Australian phase 1 study next month and thus become EtiraRx’s first clinical-stage project. LIPA encodes lysosomal acid lipase, and was identified as the target of ERX-315, the lead in a series of molecules EtiraRx was working on for endocrine therapy-resistant breast cancer.

Finally, investors in Compass Therapeutics will note the entry into phase 1 of 3SBio/Sunshine Biopharma’s SSGJ-706, a MAb attempting to block PD-1 and PD-L1. Compass is developing the similarly acting bispecific CTX-8371, which the company says aims to eliminate PD-1 from effector cells rather than inhibiting PD-1/PD-L1 interaction, and which entered phase 1 a few months ago.

Lilly has clinically studied the anti-PD-1 x PD-L1 bispecific LY3434172, while BeiGene combined Tevimbra with the anti-PD-L1 MAb BGB-A333, but neither approach seems to be in active development.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 29 Jul and 1 Aug 2024.